Enhanced dissolution rate of nimodipine through β-lactoglobulin based formulation

Amorphous solid dispersions (ASD) have been considered as one of the most effective strategies to increase solubility and dissolution rate of poorly water-soluble drugs. Carriers, in which the poorly water-soluble drug is dispersed, contribute a large extent to the solid-state properties, stabilities and dissolution performance of ASDs. This study investigated the solid-state properties, physical stability, and in vitro dissolution behaviour of nimodipine ASDs formulated with a traditional polymeric carrier, i.e., polyvinylpyrrolidone (PVP) and a novel carrier, i.e., β-lactoglobulin (BLG). The ASDs with both carriers were prepared using ball milling as preparative technique at 10%, 17.5%, 25%, 30% and 40% drug loadings (DLs). All the formulations were found to be amorphous upon milling for 60 min based on X-ray powder diffraction measurements, however, the ASDs were found to be homogeneous unequivocally only at DLs below 25%. After open storage at accelerated conditions (40 °C/75% relative humidity), only the ASDs formulated with BLG at 10% and 17.5% DLs maintained the amorphous form. The dissolution study revealed that all the freshly prepared ASDs formulated with PVP and the ASDs formulated with BLG at or above 25% DLs, showed a low drug release (< 30 µg/mL in simulated gastric fluid, < 70 µg/mL in simulated intestinal fluid). Whilst the ASD formulated with BLG at 10% DL exhibited a high drug release with a maximum concentration (Cmax) of 251 µg/mL in simulated gastric fluid and 231 µg/mL in simulated intestinal fluid. Surprisingly, the ASD formulated with BLG at 17.5% DL demonstrated an even higher drug release (Cmax, 643 µg/mL in simulated gastric fluid, 332 µg/mL in simulated intestinal fluid), compared to the ASD of 10% DL. These findings underline the importance of rationally investigating both carrier types and DL in the design of ASDs, in order to obtain a stable ASD with the desired enhanced dissolution rate of poorly water-soluble drugs.